The focus of Dr. Fatatis’s research is the identification of novel biomarkers and therapeutic targets for the management and therapy of metastatic disease. His lab is particularly interested in the dissemination and growth of cancer cells in secondary organs such as skeleton, lungs and brain.
The laboratory pursues a translational approach by employing cellular and molecular biology techniques combined with pre-clinical models of cancer growth and dissemination. Particular emphasis is placed on mechanism of activation and downstream signaling of both tyrosine kinase and G protein-coupled receptors.
A first line of investigation concerns the functional interactions between the chemokine fractalkine and its receptor CX3CR1. Dr. Fatatis’s lab was the first to report the expression of CX3CR1 by both prostate and breast cancer cells and its chemokine ligand by the bone stroma. In addition, his group showed that this chemokine-receptor pair is implicated in both adhesion of cancer cells to the endothelial wall of the bone marrow sinusoids and their extravasation in the surrounding tissue.
Through collaborative efforts the lab is currently screening novel small-molecule inhibitors of CX3CR1 with the ultimate intent of identifying compounds that effectively counteract the seeding of prostate and breast cancer cells at the skeletal level.
A second major project is focused on the identification of molecular factors supporting the survival and growth of disseminated cancer cells and their progression into metastatic lesions.
Dr. Fatatis’s group reported that bone-metastatic prostate cancer cells express high levels of alpha receptor for platelet-derived growth factor (PDGFR) and that targeting PDGFR with a humanized monoclonal antibody reduces bone metastases by 70% in animal models. Based on the strong evidence provided by their pre-clinical data, Eli Lilly is currently conducting phase II clinical trials with the antibody IMC-3G3 (Olaratumab) for advanced prostate adenocarcinoma.
Furthermore, the lab has also identified PDGFR-regulated genes that directly induce metastatic behavior in prostate cancer cells and represent potential therapeutic targets to counteract metastatic disease.